Method for producing protein microspheres
First Claim
1. A method for producing protein microspheres comprising the steps of:
- a) contacting a prolamine solution, wherein the prolamine solution contains at least one type of prolamine and a compound to be incorporated into the microspheres, with a second liquid, wherein the second liquid is of limited miscibility with the prolamine solvent such that the second liquid does not form a stable homogeneous solution with the prolamine solvent and does not dissolve the prolamine, in a ratio of prolamine solution to second liquid of at least 1;
20, to form a prolamine-non-solvent mixture;
b) agitating the prolamine-non-solvent mixture to form a dispersion of the prolamine solution in the second liquid at a temperature of less than about 65°
C.; and
c) removing the prolamine solvent to form stable prolamine microspheres without crosslinking or heat denaturation.
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Abstract
Protein microspheres are formed by phase separation in a non-solvent followed by solvent removal. The preferred proteins are prolamines, such as zein, that are hydrophobic, biodegradable, and can be modified proteolytically or chemically to endow them with desirable properties, such as a selected degradation rate. Composite microspheres can be prepared from a mixture of proteins or a mixture of proteins with one or more bioerodible polymeric materials, such as polylactides. Protein coatings can also be made. Compounds are readily incorporated into the microspheres for subsequent release. The process does not involve agents which degrade most labile proteins. The microspheres have a range of sizes and multiple applications, including drug delivery and delayed release of pesticides, fertilizers, and agents for environmental cleanup. Selection of microsphere size in the range of less than five microns and mode of administration can be used to target the microparticles to the cells of the reticuloendothelial system, or to the mucosal membranes of the mouth or gastrointestinal tract. Larger implants formed from the microspheres can also be utilized, especially for agricultural applications.
409 Citations
20 Claims
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1. A method for producing protein microspheres comprising the steps of:
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a) contacting a prolamine solution, wherein the prolamine solution contains at least one type of prolamine and a compound to be incorporated into the microspheres, with a second liquid, wherein the second liquid is of limited miscibility with the prolamine solvent such that the second liquid does not form a stable homogeneous solution with the prolamine solvent and does not dissolve the prolamine, in a ratio of prolamine solution to second liquid of at least 1;
20, to form a prolamine-non-solvent mixture;b) agitating the prolamine-non-solvent mixture to form a dispersion of the prolamine solution in the second liquid at a temperature of less than about 65°
C.; andc) removing the prolamine solvent to form stable prolamine microspheres without crosslinking or heat denaturation. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20)
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Specification